Long-term follow-up after surgery in localized laryngeal amyloidosis

To study effectiveness of surgery and watchful waiting in localized laryngeal amyloidosis, retrospective case series. This retrospective study comprises all consecutive patients with localized laryngeal amyloidosis surgically treated in a tertiary hospital between 1994 and February 2016. Recurrence rate, revision surgery, progression to systemic amyloidosis, and changes in voice were monitored yearly. Eighteen patients were included. Seven women and eleven men had a median age 50 years (range 21-77 years) and median follow-up 6.4 years (2.4-17 years). Amyloid was located in subglottis (5), glottis (8), false vocal folds (8) and other supraglottic areas (5), in more than one laryngeal region (13) and bilaterally (12). Cold steel excision was used at the glottis; CO2 laser excision, sometimes assisted by microdebrider, at other laryngeal areas. Eleven patients needed revision surgery, ten within the first 4 years after surgical treatment. One patient needed his first revision surgery after 11 years. Five patients needed a second revision within 6 years after initial diagnosis. Two patients needed a third revision. Indications for first revision surgery were progression (8) with dysphonia (7), dyspnea (2), dysphagia (1), exclusion of malignancy (1), and aphonia (1). No patient developed systemic amyloidosis during follow-up. Although local progression of amyloid necessitates revision surgery once or twice in the first 4-6 years, progression slows down thereafter. Late progression, however, remains possibl

Estimating the fiscal impact of rare diseases using a public economic framework:a case study applied to hereditary transthyretin-mediated (hATTR) amyloidosis

Background A wide range of rare diseases can have fiscal impacts on government finances that extend beyond expected healthcare costs. Conditions preventing people from achieving national lifetime work averages will influence lifetime taxes paid and increase the likelihood of dependence on public income support. Consequently, interventions that influence projected lifetime work activity, morbidity and mortality can have positive and negative fiscal consequences for government. The aim of this study was to apply a public economic framework to a rare disease that takes into consideration a broad range of costs that are relevant to government in relation to transfers received and taxes paid. As a case study we constructed a simulation model to calculate the fiscal life course of an individual with hereditary transthyretin-mediated (hATTR) amyloidosis in The Netherlands. In this lethal disease different progressive disease scenarios occur, including polyneuropathy and/or cardiomyopathy. Results Due to progressive disability, health care resource use, and early death, hATTR amyloidosis with polyneuropathy receives more transfers from government compared to the general population. In a scenario where a patient is diagnoses with hATTR at age 45, an individual pays €180,812 less in lifetime taxes and receives incrementally €111,695 in transfers from the government, compared to a person without hATTR. Patients suffering from cardiomyopathy die after median 4 years. The health costs of this scenario are therefore lower than that of the other polyneuropathy-based scenarios. Conclusions The fiscal analysis illustrates how health conditions influence not only health costs, but also the cross-sectorial public economic burden attributed to lost tax revenues and public disability allowances. Due to the progressive nature of hATTR amyloidosis used in this study, public costs including disability increase as the disease progresses with reduced lifetime taxes paid. The results indicate that halting disease progression early in the disease course would generate fiscal benefits beyond health benefits for patients. This analysis highlights the fiscal consequences of diseases and the need for broader perspectives applied to evaluate health conditions. Conventional cost-effectiveness framework used by many health technology assessment agencies have well-documented limitations in the field of rare diseases and fiscal modeling should be a complementary approach to consider

Imaging cardiac innervation in amyloidosis

Cardiac amyloidosis is a form of restrictive cardiomyopathy resulting in heart failure and potential risk on arrhythmia, due to amyloid infiltration of the nerve conduction system and the myocardial tissue. The prognosis in this progressive disease is poor, probably due the development of cardiac arrhythmias. Early detection of cardiac sympathetic innervation disturbances has become of major clinical interest, because its occurrence and severity limits the choice of treatment. The use of iodine-123 labelled metaiodobenzylguanidine ([I-123]MIBG), a chemical modified analogue of norepinephrine, is well established in patients with heart failure and plays an important role in evaluation of sympathetic innervation in cardiac amyloidosis. [I-123]MIBG is stored in vesicles in the sympathetic nerve terminals and is not catabolized like norepinephrine. Decreased heart-to-mediastinum ratios on late planar images and increased wash-out rates indicate cardiac sympathetic denervation and are associated with poor prognosis. Single photon emission computed tomography provides additional information and has advantages for evaluating abnormalities in regional distribution in the myocardium. [I-123]MIBG is mainly useful in patients with hereditary and wild-type ATTR cardiac amyloidosis, not in AA and AL amyloidosis. The potential role of positron emission tomography for cardiac sympathetic innervation in amyloidosis has not yet been identified

Echocardiographic features of an atypical presentation of rapidly progressive cardiac amyloidosis

We present the case of a 66 year old male who presented with dyspnea and reduced exercise tolerance. Echocardiography demonstrated impaired left ventricular (LV) function and restrictive diastolic function with pronounced concentric left ventricular hypertrophy (LVH) without a history of hypertension and no aortic valve stenosis. Differential diagnostics of concentric LVH are discussed in detail. In the current case, cardiac amyloidosis (AL) amyloidosis was diagnosed and confirmed by serum amyloid P (SAP) scintigraphy and abdominal fat aspiration biopsy. This case shows the rapid decline in clinical condition with progression of cardiac involvement of AL. As discussed in detail, cardiac involvement in AL-amyloidosis generally denotes a poor prognosis, regardless of the method of treatment

A real-life cohort study of immunoglobulin light-chain (AL) amyloidosis patients ineligible for autologous stem cell transplantation due to severe cardiac involvement or advanced disease

Objective: To study the outcome of patients with AL amyloidosis who were ineligible for high dose melphalan (HDM) and autologous stem cell transplantation (ASCT).Methods: A real-life retrospective observational cohort study of Dutch patients with AL amyloidosis ineligible for HDM and ASCT was performed at the University Medical Center Groningen from January 2001 until April 2017. Primary outcome measure was overall survival (OS). Secondary outcome measures were hematological response (HR), organ responses, and treatment toxicity.Results: Eighty-four patients were included. Ineligibility was due to NYHA class III/IV (n = 58), otherwise advanced disease (n = 11), advanced age (n = 14), or treatment refusal (n = 1). Early death (<3 months) rate was high (44%). Median OS improved from 4 months in period 2001-2009 (n = 36) to 8 months in period 2009-2017 (n = 48, p = .02). HR was seen in 29%, and 42% of the patients, respectively. Median OS was 36 months after induction treatment with bortezomib (n = 32) and 18 months with immunomodulatory imide drug (IMID) (n = 16), both higher than median OS (7 months) with other regimens (n = 27). Incidence of toxicity was high (51%).Conclusion: OS improved in this high-risk group over the years, especially after introduction of new treatment modalities. However, early death rate remains high, illustrating the need for more effective treatment